Chapter 1
Food and Agricultural Biotechnology: An Overview 1
Daniel D. Jones and Alvin L. Young
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Office of Agricultural Biotechnology, Cooperative State Research, Education, and Extension Service, U.S. Department of Agriculture, 14th Street and Independence Avenue, Southwest, Washington, DC 20250-0904 Biotechnology is an invaluable process for the quick, safe, and precise transfer of specific genetic information from one organism to another, in order to create predictable end results. As such, biotechnology represents a tool that is an important component of a balanced, efficient, well-managed, and environmentally responsible agricultural system, which uses the very best of technology and science. Recent discoveries in the field of biotechnology have made the life sciences some of the most exciting fields of scientific endeavor--especially for those with creativity and vision. This overview provides a "sampling" of how biotechnology will impact global agriculture, and hence, the world population of the third millennium. For centuries, people have sought to improve plants and animals and food products derived from them by selecting and breeding individuals that excel in some desirable property or characteristic. The usual goals of traditional breeding have been to develop plants and animals that grow faster, produce more, provide better quality products, use resources more efficiently, and show increased fertility or resistance to disease and stress. The tools and techniques provided by modern biotechnology do not change these traditional goals of agriculture. Instead, they offer new opportunities for changing biological traits in a much more direct, predictable, and timely manner than is possible with conventional plant and animal breeding. Several products of modern biotechnology are now on the market (7). They include recombinant chymosin for use in cheese-making, recombinant bovine somatotropin for increasing feed efficiency in dairy cattle, and antisense tomatoes that can be picked ripe and have a longer shelf-life. Many more products of food and agricultural biotechnology are in the development pipeline and they should begin appearing on supermarket shelves in the coming months and years (7,2). The Federal government recently released a report entitled Biotechnology for the 21st Century: New Horizons (3). In it are described emerging biotechnology 1
Corresponding author This chapter not subject to U.S. copyright Published 1996 American Chemical Society
Takeoka et al.; Biotechnology for Improved Foods and Flavors ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
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research opportunity areas in agriculture, the environment, manufacturing/bioprocessing, and marine biotechnology and aquaculture. The report outlines agricultural research opportunities in five areas: 1) genome mapping in plants, animals, and microbes; 2) biochemical and genetic control of metabolic pathways; 3) the molecular basis of growth and development in plants and animals; 4) the molecular basis of interactions of plants and animals with their physical and biological environments; and 5) enhancement of food safety through development of molecular probes, biosensors, and microbial ecological control methods (3). The purpose of this review is to survey recent developments in several areas of food and agricultural biotechnology. These areas include plant biotechnology, animal biotechnology, aquaculture, genome mapping, food safety, diet and nutrition, functional foods, and patenting. Several of these issues have also received extensive coverage in the science press (4). Plant Biotechnology USDA has issued permits and ackowledgements for testing genetically engineered plants in thousands of field test sites (5). Six plant species accounted for about 85 percent of the approved field tests; tobacco, tomato, potato, corn, soybean, and cotton. The early genetic changes were largely single-gene changes such as herbicide tolerance, insect resistance, virus resistance, and fungus resistance. Now a wider variety of genetic changes in product quality is being tested including: delayed ripening in tomatoes, peas, and peppers; modified oils, enzymes, and storage proteins; higher solids content in tomato and potato; improved nutrition in corn, sunflower, soybean, and oilseeds; and freeze tolerance in tomatoes and other fruits and vegetables (2). Many transgenic plants field tested heretofore have involved only one or a few gene changes. Current research on genome mapping and gene regulation will facilitate the future manipulation of whole clusters of genes that influence agronomic and other economically important traits. Multi-gene traits in plants that may be amenable to the methods of biotechnology include improvements in photosynthesis, nitrogen fixation, heat tolerance, drought tolerance, cold tolerance, and salt tolerance. For example, scientists have transferred a gene for salt tolerance from an Old World plant called "ice plant" to tomato, tobacco, and Arabidopsis thaliana (3,6,7). The ability to clone ion transport genes and their genetic regulatory sequences from salttolerant plants such as ice plant and mangrove could lead to more crop species better able to withstand salt build-up from irrigated soils with poor drainage. Another plant biotechnology development with implications for agricultural production is the use of plants as bioreactors to produce valuable substances which are then isolated from the plant and marketed. A recent example is transgenic tobacco that produces human glucocerebrosidase (hGC), an enzyme used in the treatment of Gaucher's disease (8). A single clinically useful dose of hGC has previously taken thousands of human placentae or Chinese hamster ovary cells, thus contributing to the high cost of the drug. Other examples of exogenous substances from transgenic plants include engineered antibodies in transgenic tobacco (9) footand-mouth disease antigen in transgenic cowpea (70,77), and rabies virus glycoprotein in transgenic tomatoes (72). A number of companies appear to be
Takeoka et al.; Biotechnology for Improved Foods and Flavors ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
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Food and Agricultural Biotechnology: An Overview 3
working on the production of enzymes, therapeutics, and vaccines from transgenic tobacco (72), but there is uncertainty that tobacco "pharming" will be a profitable endeavor for traditional tobacco farmers (73).
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Animal Biotechnology Animal biotechnology can lead to improvements in growth and feed efficiency, animal health, growth and development, reproductive efficiency, food product quality, and lactational production of novel or valuable proteins. One of the greatest advantages of transgenic animal technology is that it can produce specific, significant genetic changes that are not constrained by existing genetic variation in the host population (14). For technical and economic reasons, animal biotechnology is proceeding at a somewhat slower pace than plant biotechnology. Early experiments involved the use of animal growth hormones, administered either by repeated injection or by genetic incorporation, to improve feed efficiency and growth rate (75). Repeated injection is very labor-intensive and the success rate of most current methods of genetic incorporation is disappointingly low (75). Consequently, animal scientists are looking for better methods of transferring genetic material and for controlling the expression of genetic material once it is incorporated into a host animal. Growth Hormones. One of the more controversial areas of animal biotechnology has been the administration of bovine somatotropin (BST) to cows to increase the efficiency of milk production. This development has posed issues of both food safety and food labeling. The Food and Drug Administration (FDA) concluded in 1993 that milk from cows treated with recombinant BST (rBST) is safe for human consumption (76). The FDA approval was based on over 100 studies of the human food safety of BST (17). The use of rBST posed difficult food labeling issues for dairy products. The FDA concluded that it did not have a statutory or scientific basis for requiring special labeling of dairy products from rBST-treated cows. Food companies, however, may voluntarily label dairy products from rBST-treated cows provided the information is truthful and not misleading (16). Some companies have seen more market value in milk from cows not treated with rBST. FDA also permitted special labeling for milk from untreated cows as long as the labeling was truthful and not misleading (18). Some authors have focused on opportunities for genetic manipulation of dairy cattle beyond BST (79). Opportunities include production of heterologous proteins in milk (20,21), modification of milk and milk protein composition (22,23), and genetic modification of the rumen or intestinal microflora of cows to improve their digestive capacity, feed efficiency, or ability to degrade plant toxicants (24,25). Scientists have also begun to think about transgenic arthropods as a component of pest control programs (26). Contained research on transgenic insects is in progress in many laboratories around the world (27) and it may lead to advances in the control of insect pests as well as to help for beneficial insects such as bees.
Takeoka et al.; Biotechnology for Improved Foods and Flavors ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
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Aquaculture Aquaculture, the cultivation of certain aquatic animals and plants in farms on land and at sea, offers a partial solution to growing global consumption of fish and declining natural fishery populations. The World Bank estimates that aquaculture could meet some 40 percent of the demand for fish within 15 years if the proper investments in research and technology are made by governments today (28). Those practicing aquaculture have to contend with the same problems that any farmer faces: disease, pollution, space limitations, volatile markets, and unintended effects on the environment. Genetic engineering offers a promising approach to managing many of these problems (3). China, for example, has 10 million farmers engaged in the annual production of 21 million metric tons of fish. The government of China has announced that their goal for the next five years (1996-2000) is to increase production to 30 million metric tons. The application of biotechnology to enhance growth, feed efficiency, and reproduction will be essential in meeting this goal (29). International organizations have also begun the process of developing criteria for evaluating the food safety of products of aquaculture (30). Some people are also very concerned about the potential environmental effects of aquaculture operations. A USD A advisory committee on aquatic biotechnology and environmental safety recently drew up a set of performance standards and logic flowcharts for safely conducting research with genetically modified fish and shellfish (ABRAC). This effort was especially noteworthy because it enjoyed the collective support of the aquatic research community, private industry, environmental interest groups, and state natural resource officials. Genome Mapping Genome mapping is an ongoing scientific effort that will provide useful background information for genetic modification of plants and animals. Just as improvements in mapmaking contributed to the age of world exploration in the 15th and 16th centuries, so will genome mapping make significant contributions to the breeding of plants and animals and the improvement of foods derived from them. Since the mid-1980's, scientists have been able to construct maps of the genetic makeup of various organisms. Programs of genome mapping for economically important traits have been initiated. Genome maps for several agronomically important species are near completion. These maps offer tremendous opportunities for researchers to pinpoint the genetic sequences that control specific traits (31). USDA supports genome research programs in both plants and animals. In the plant area for FY 1994, for example, USDA awarded about $12 M in grants to over 100 investigators to map all or part of the genomes of over 50 species of plants (32). USDA also supports an animal genome mapping project although not as many species are involved as in the plant area. Agricultural Experiment Stations associated with many of the Land Grant Universities have also recognized the importance of investing in genome programs that involve species to state economies (31).
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Genetically Engineered Foods Biotechnology permits the transfer of the genetic material that codes for desirable traits from one organism, variety, or species to another to produce transgenic plants and animals. These technologies have the potential to improve the productivity and quality of many foods. In May, 1994, the Food and Drug Administration concluded that FLAVR SAVR, a new variety of tomato developed through biotechnology, is as safe as tomatoes bred by conventional means (33). The FLAVR SAVR tomato was developed by a technique called antisense in which an inverted polynucleotide segment which cannot be interpreted correctly by a cell's biosynthetic machinery is added to the cell thereby interfering with the function of the target gene. The antisense technique eliminates a tissue softening enzyme from the tomato thus slowing the biological process by which a tomato ripens and eventually rots. The tomato can thus remain on the vine longer before being harvested, yet remain firm enough to ship in a ripe state most times of the year. Genetically engineered foods were the subject of controversy since before the antisense tomato first appeared on supermarket shelves (34,35,36,37). The prospect of commercial availability of genetically engineered foods has raised questions of safety, ethics, and social acceptability in the minds of many consumers, advocacy groups, and public officials (38). Supporters of genetic engineering say these techniques will provide healthier, cheaper, better-tasting foods; reduce farmers' dependence on toxic chemicals to control weeds and pests; and increase the world's food supply to meet the needs of a growing population. In some cases, genetic engineering will provide entirely new approaches to controlling plant pathogens such as viruses. Critics say scientists do not fully understand the impact that genetic changes can have on the nutrition, toxicity, or other properties of foods. Critics fear that genetic manipulations may permit the wider spread of allergy-producing proteins in the food supply. They also fear that the artificial splicing of novel genes into agricultural plants and animals could have unintended ecological consequences such as more aggressive weeds, voracious, oversized fish, and rapidly evolving plant viruses. Federal agencies have addressed many of these concerns under various statutory authorities and other ongoing programs. For example, for early field testing of genetically engineered plants under plant pest statutes, USDA prepared detailed environmental assessments before issuing permits and these assessments were critically analyzed by outside parties (39). As the Department of Agriculture gained experience and biosafety data on field tests of engineered plants. The permit application system was largely replaced in 1993 by a notification system (40,49). Similarly, for pioneering outdoor research on transgenic fish, USDA prepared an environmental assessment that was open to public comment (42). Subsequently, a USDA advisory committee developed a set of Performance Standards for Safely Conducting Research with Genetically Modified Fish and Shellfish (43). Federal agencies have also addressed the safety of foods derived from new varieties of plants and animals. For example, the Food and Drug Administration published a statement of policy on foods derived from new plant varieties that
Takeoka et al.; Biotechnology for Improved Foods and Flavors ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
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addressed issues of potential allergenicity and changes in the content of nutrients and toxicants (44). Similarly, USDA, with the assistance of a Federal advisory committee, announced criteria for evaluating the food safety of transgenic (45) and non-transgenic (46) animals from transgenic experiments.
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Biotechnology and Food Safety Food-borne illness can become a significant threat in a large, complex food processing and distribution system. In 1993, for example, more than 500 persons in the Pacific Northwest became ill from eating undercooked hamburger and four persons died. This outbreak of food-borne illness was attributed to a pathogenic strain of the common intestinal bacterium E. coli 0157:H7 which appears to be harmless to cattle, but which can cause serious disease in humans (3). There are several ways in which the tools of biotechnology can be used to improve the safety of food products. Biotechnology can help to improve both the detection and control of food-borne microorganisms. It can do this, for example, through improved methods for detecting microbial contaminants in food and by the design of food processing enzymes that can withstand higher processing temperatures. Biotechnology offers several different technologies for improved detection of microbial agents in food products. Two of these are monoclonal antibody technology and DNA probe technology. Antibodies are protein molecules that can recognize foreign antigens to mark them for identification, removal or destruction. Monoclonal antibodies are antibodies that are produced by specialized cells in large amounts and high purities that make them very useful for a wide variety of detection applications including the analysis of food products for microbial contaminants and pesticide residues (47). A second technology for improving microbial detection in food products is DNA probes. These are carefully designed fragments of deoxyribonucleic acid (DNA) that can bind to the genetic material of viruses, bacteria, or parasites for purposes of identification, detection, or, in some cases, inactivation. DNA probe kits are available for food-borne pathogens such as Salmonella, Listeria, E. coli, and Staphylococcus aureus. These diagnostic kits have several advantages over traditional plating methods including greater precision, shorter turnaround times, and reduced need for highly trained personnel (3). An outstanding example of DNA technology is the polymerase chain reaction (PCR). This is a technique for producing millions of copies of a single DNA molecule so that it can be analyzed almost as easily as a purified chemical substance. The Food and Drug Administration has developed and deployed in its field laboratories a PCR method for the detection of Vibrio cholerae in imported food (3). Practical experience with this and other methods will no doubt highlight areas where further technical improvements can be made for purposes of food analysis. Biotechnology can also provide methods for controlling and discouraging the growth of microorganisms during food processing. Enzymes from a number of naturally occurring organisms, such as those living around ocean-floor hydrothermal vents, are stable under conditions of high temperature and high acidity that kill or inactivate many other microorganisms. Some of these enzymes show great promise for food processing applications, and several companies have started to market thermostable enzymes for that purpose (48). Takeoka et al.; Biotechnology for Improved Foods and Flavors ACS Symposium Series; American Chemical Society: Washington, DC, 1996.
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7 Food and Agricultural Biotechnology: An Overview
Biosensors. Another exciting area for food biotechnology is the development of biosensors. These are devices with special surfaces or membranes that can respond to the presence of a specific substance or cell type in a food or other substance. Depending on how the device is designed, its use could be as simple as placing the device in contact with the food product and reading the amount of the specific substance from a meter or dial. Biosensors are commercially available to detect a variety of sugars, alcohols, esters, peptides, amino acids, cell types, and antibiotics (49,50). Miniaturization and mass production of biosensors could increase their availability and decrease their unit cost. Technologies such as microlithography, ultrathin membranes, and molecular self-assembly have the potential to facilitate the development and diversification a wide variety of biosensors. Miniature biosensors could be incorporated into food packages to monitor temperature stress, microbial contamination, or remaining shelf life, and to provide a visual indicator to consumers of product state at the time of purchase (3,51,52). Biotechnology, Diet, and Nutrition The link between diet, the maintenance of health, and the development of chronic disease has become increasingly evident in recent years. Many consumers are looking for inexpensive and readily available food products that meet their requirements for less fat, more nutrients, and fewer additives. The technologies of the new biotechnology hold great promise for helping nutritionists and physicians to explore the design of new foods to meet dietary and health goals, particularly for subpopulations such as children (53). An example is the improvement of the nutritional attributes of animal products through decreases in fat, saturated fatty acids, and cholesterol. Porcine somatotropin (PST), for example, may help to improve human health, while at the same time lowering the farmer's cost of production. PST not only improves the feed efficiency in hogs by 25 to 30 percent - but, perhaps more importantly in this age of health consciousness, it reduces fat deposition, allowing PST-treated hogs to provide consumers with leaner cuts of pork (54). This ability to produce lean pork has important implications for improving human health by reducing dietary fat and cholesterol. As producers of animal products begin to understand more about how diet relates to health and to implement appropriate feeding, breeding, and selection programs, biotechnology offers them a valuable set of tools. Functional Foods. "Functional food" may be broadly defined as any modified food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains (55). Other terms sometimes used include "nutraceutical" and "designer food" which usually denote a processed food that is supplemented with food ingredients naturally rich in disease-preventing substances (55). These diseasepreventing substances include phytochemicals, substances found in fruits and vegetables that exhibit a potential for modulating human metabolism in a manner favorable for disease prevention.
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The National Cancer Institute, through its Experimental Food Program, has identified many phytochemicals that can interfere with and potentially block the biochemical pathways that lead to malignancy in animals. These phytochemicals include sulfides, phytates, flavonoids, glucarates, carotenoids, coumarins, terpenes, lignans, phenolic acids, indoles, isothiocyanates, and polyacetylenes. Foods that appear to contain significant amounts of these phytochemicals include garlic, onions, broccoli, cabbage, soybeans, citrus fruits, cereal grains, and green tea (56). Biotechnology is only one method of producing functional foods (57), but it is one that may find favor among producers in the future because of its molecular precision, genetic specificity, and relative speed. Downloaded by 79.98.107.90 on April 9, 2016 | http://pubs.acs.org Publication Date: August 13, 1996 | doi: 10.1021/bk-1996-0637.ch001
Biotechnology and the Environment The application of biotechnology to environmental problems is one of its areas of greatest potential. Biotechnology has already contributed to a safer environment, with many anticipated breakthroughs on the horizon. A few examples of areas where biotechnology has already had an impact include the replacement of environmentally hazardous pesticides with safer biotechnologically-produced pesticides, the development of new microbial techniques for cleaning up pollution, the creation of alternative fuels that are less environmentally damaging, and the formulation of new biodegradable materials (3). Biosystems developed through biotechnology research can be used to treat contaminated wastes, oil spills, acid wastes, municipal wastes, and pesticides. Bioremediation is a biological conversion process in which living organisms assimilate and store waste byproducts such as toxic materials, heavy metals, uncollected residues from oil spills, and other pollutants that endanger the environment. Genetic engineering promises to dramatically expand our ability to create microbes that will break down a wider range of wastes (3). Plants can also be used to absorb heavy metals through their roots thus helping to cleanse contaminated soils (58). Biotechnology promises to expand the set of tools at our disposal for control of pests in agricultural production systems. Natural and engineered microbial pesticides are being developed to control a variety of lepidopteran pests (59). Some of these biological pesticides may act as replacements for environmentally persistent chemicals, quickly breaking down into harmless components and thus reducing residue problems. Biotechnology research is seeking to develop new foods, feeds, fiber, and biomass energy production processes that are environmentally safe. Researchers are developing new uses for agricultural products to replace non-renewable sources of raw materials. Their work promises to have broad commercial applications and has already led to the creation of new industries. These discoveries have led to environmentally compatible commercial products such as biodegradable plastics (60), soybean oil printing inks, and super absorbent polymers (67). Biotechnology techniques such as gene amplification, DNA probes, bioluminescence, and immunological assays also are being used to increase our understanding of the complexities of agricultural production and the environment.
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It is clear that biotechnology research will become increasingly significant in global efforts to improve agricultural production and protect the environment.
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Patenting A patent is a limited monopoly that protects the interests of an inventor by excluding others from practicing an invention for a specified period of time. Patenting of biotechnology inventions is necessary, in the view of some, to provide incentive for investing time, money, and resources in product research and development (62). In the view of others, patenting biotechnology inventions, particularly living organisms, raises serious ethical and religious concerns (63). In addition, many scientists are concerned about the chilling effect of overly-broad patents on the progress of scientific research (64). And farmers are concerned about exempting on-farm uses of a patented product from royalty payments (65). Finally, there are difficult international questions involving developing countries (66) and the effects of patents on international trade (67). Conclusion Our ability to manipulate genetic material for biomedical, agricultural, and environmental purposes represents a major technological advance. Biotechnology can have a dramatic impact on the agriculture and food producing sector. It has the potential to reduce the need for agricultural chemicals; improve the productivity, efficiency, and profitability of food production and processing; open new markets for improved or unique processed food products; and, improve the nutritional quality, safety, cost, and convenience of consumer food products. Literature Cited 1. 2. 3.
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